Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity
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Published:2022-01-24
Issue:5
Volume:119
Page:
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ISSN:0027-8424
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Container-title:Proceedings of the National Academy of Sciences
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language:en
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Short-container-title:Proc. Natl. Acad. Sci. U.S.A.
Author:
Fuller Carl W.1, Padayatti Pius S.1ORCID, Abderrahim Hadi1, Adamiak Lisa1, Alagar Nolan1, Ananthapadmanabhan Nagaraj1, Baek Jihye1, Chinni Sarat1, Choi Chulmin1, Delaney Kevin J.1, Dubielzig Rich1, Frkanec Julie1, Garcia Chris1, Gardner Calvin1, Gebhardt Daniel1, Geiser Tim1, Gutierrez Zachariah1, Hall Drew A.12, Hodges Andrew P.1, Hou Guangyuan1, Jain Sonal1, Jones Teresa1, Lobaton Raymond1, Majzik Zsolt1, Marte Allen1, Mohan Prateek1, Mola Paul1, Mudondo Paul1, Mullinix James1, Nguyen Thuan1, Ollinger Frederick1, Orr Sarah1, Ouyang Yuxuan1, Pan Paul1, Park Namseok1, Porras David1, Prabhu Keshav1, Reese Cassandra1, Ruel Travers1, Sauerbrey Trevor1, Sawyer Jaymie R.1, Sinha Prem1, Tu Jacky1, Venkatesh A. G.1, VijayKumar Sushmitha1, Zheng Le1, Jin Sungho3, Tour James M.4, Church George M.5ORCID, Mola Paul W.1, Merriman Barry1
Affiliation:
1. Roswell Biotechnologies Inc., San Diego, CA 92121 2. Department of Electrical Engineering, University of California, San Diego, CA 92093 3. Department of Materials Science, University of California, San Diego, CA 92093 4. Department of Chemistry, Rice University, Houston, TX 77005 5. Department of Genetics, Harvard Medical School, Boston, MA 02115
Abstract
For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.
Funder
ODNI | Intelligence Advanced Research Projects Activity
Publisher
Proceedings of the National Academy of Sciences
Subject
Multidisciplinary
Cited by
36 articles.
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